Plain language summary
Mild cognitive impairment (MCI) is a characterised by a decline in cognitive function between normal aging and the development of dementia. While brain atrophy occurs in normal aging, patients with MCI or dementia exhibit much higher rates of atrophy. Results from a recent trial demonstrated that homocysteine-lowering B vitamins resulted in a significant reduction in brain atrophy rates, and links between omega-3 fatty acids and homocysteine have been suggested. The purpose of this study was to investigate whether plasma omega-3 fatty acid concentrations modify the treatment effect of B vitamins on brain atrophy rates among 168 elderly adults with MCI. Participants were randomly assigned to receive placebo or high-dose vitamin B supplementation and both brain scans and plasma concentrations were done at baseline and 2 years. The findings of this study demonstrated that, in patients with high omega-3 plasma concentrations, B vitamin supplementation slowed brain atrophy by 40% compared with those in the placebo group. This indicates that the effect of B vitamin supplementation on brain atrophy rates depend on plasma omega-3 fatty acid concentrations.
Abstract
BACKGROUND Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia. OBJECTIVE We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG). DESIGN This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations. RESULTS There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 μmol/L). High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group. CONCLUSIONS The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials. This trial was registered at www.controlled-trials.com as ISRCTN94410159.
Methodological quality
Jadad score
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4
Allocation concealment
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Yes
